Several well publicized incidents have occurred in which patients have contracted virulent forms of common infectious organisms. These organisms (the so-called "flesh eating bacteria"), it is believed, produce proteolytic enzymes and can cause soft tissue infections known as necrotizing fasciitis.
Patients infected with these organisms often experience vascular thrombosis and ischemic gangrene of the underlying tissue in the affected area. Left untreated, the condition spreads rapidly in the body's tissues leading to amputation and, in some cases, death. In addition, diagnosis is difficult because the infection's symptoms often mimic those of cellulitis, a disorder which calls for a very different course of treatment.
The effective treatment of necrotizing fasciitis is often problematic. Conventional treatments involve the use of one or more of: antibiotics, minerals, vitamins, hyperbaric oxygen, surgical abridgement and, as a last resort, amputation. In American Family Physician, vol. 56, No. 1, (July, 1997), pages 145-49, Drs. D. L. Meltzer and M. Kabongo describe a necrotizing fasciitis case and discuss a treatment regime which includes a combination of several of these.
It is believed that proteolytic enzyme producing bacteria, such as Streptococci, Staphylococci and Escherichia coli organisms, to name a few, are generally responsible for the current increase in incidences of these virulent infections.
Streptoccus viridans, a common bacteria, is believed to be one of these virulent, "flesh-eating" bacteria. When Strep. viridans is present, the destruction of tissue is mediated via the action of the proteolytic enzyme which the organism has produced.
While proteolytic enzymes are believed to be involved in the action of these bacterial infections, they are not usually treated with protease inhibitors.
Protease inhibitors, along with reverse transcriptase inhibitors (e.g., didanosine and zidovudine), are commonly used to treat patients having compromised immune systems due to retroviral infections, such as human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). U.S. Pat. Nos. 5,196,438 and 5,413,999 discuss the use of the protease inhibitor drugs saquinavir and indinavir to treat retroviruses.
In HIV treatment, protease inhibitors retard the production of HIV protease, the enzyme responsible for processing HIV genes that form protein products when infectious viral particles spread. Thus, protease inhibitors cause the production of immature, noninfectious viral particles and help curb the spread of HIV throughout the host's body. See A. Pakyz and D. Israel, "Overview of Protease Inhibitors", in Journal of American Pharmaceutical Association, vol. NS37, No. 5, pages 543-51 (September/October 1997).
While research has been done on their effectiveness in treating HIV and AIDS, the use of protease inhibitors to treat infections other than retroviruses has not been widespread. This invention deals with such use.
The invention provides a simple and effective method of inhibiting the effects of the proteolytic enzymes produced by non-retroviral organisms, while a treatment regimen is worked out to eradicate the organisms in those affected.